Acetic Acid → N-(4-(2,4-difluorophenoxy)phenyl)-1-pyrid-3-ylethylamine

Participants

Reaction Steps

A solution of N-(4-(2,4-difluorophenoxy)phenyl)amine (1.0 equiv.) in dichloromethane (0.2 M) was cooled to 0° C. and treated with 3-acetylpyridine (Aldrich; 1.4 equiv.), acetic acid (5.0 equiv.), and sodium triacetoxyborohydride (2.5 equiv.). The reaction was allowed to warm to ambient temperature and stirred an additional 22 hours. The reaction was cautiously quenched with saturated aqueous NaHCO3 then adjusted to pH=10 with 1 N NaOH. The mixture was stirred for 4 hours then the layers were separated. The aqueous layer was extracted twice with DCM. The combined organics were washed with brine, dried over sodium sulfate, filtered, and concentrated. The crude material was purified via radial chromatography eluting with 50:50 to 60:40 ethyl acetate/hexanes to give N-(4-(2,4-difluorophenoxy)phenyl)-1-pyrid-3-ylethylamine. 1H NMR (400 MHz) 1.54 (3H, d, J=6.7 Hz), 3.96 (1H, bs), 4.48 (1H, q, J=6.7 Hz), 6.44 (2H, m), 6.76 (2H, m), 6.83-6.93 (2H, m), 7.24 (1H, m), 7.44 (1H, m), 7.68 (1H, td, J=1.8, 7.9 Hz), 8.50 (1H, d, J=3.8 Hz), 8.64 (1H, bs). HRMS calcd 327.1309. Found 327.1308.

Provenance & Evidence